The effects of diabetes on the function and metabolism of the heart has been investigated in rats where diabetes was induced by injection of alloxan and the mechanical function and metabolism of the heart was determined in vitro. Acute diabetes was found to reduce the maximum capacity of the heart to develop pressure and to render the heart more susceptible to ischemia. Hearts from diabetic animals oxidized fatty acids at a faster rate than normal hearts and utilized glucose at a slower rate. Diabetic hearts had a higher level of acyl CoA and acyl carnitine esters which persisted in the in vitro perfused hearts for up to 60 minutes of perfusion with a buffer containing only glucose as substrate. Whole tissue levels of CoA were increased and levels of carnitine were decreased. These changes in CoA and carnitine were evident as early as 24 hours after induction of diabetes and were still present for a least 21 days following induction of diabetes.